Department of Occupational Health (Key Laboratory of Electromagnetic Radiation Protection, Ministry of Education), Third Military Medical University, Chongqing 400038, China.
Surgery Department of Galactophore, Zhuzhou Hospital Affiliated to Xiangya Shool of Medicine, Central South University, Zhuzhou 412000, Hunan, China.
Ecotoxicol Environ Saf. 2022 Dec 1;247:114270. doi: 10.1016/j.ecoenv.2022.114270. Epub 2022 Nov 3.
Cadmium (Cd), which is considered an endocrine disruptor, has been linked to the onset of breast cancer (BC). Our recent study demonstrated that Cd-induced BC progression has a strong correlation with miR-374c-5p dysregulation. The aim of our work was to investigate other potential miRNAs involved in Cd-induced BC cell proliferation and metastasis. In our study, the miRNA profiles of Cd-treated T-47D cells (10 μM, 72 h) were analyzed by miRNA-seq, and our results confirmed that miR-3614-5p was the top downregulated miRNA. Moreover, miR-3614-5p mimic transfection significantly decreased the proliferative ability, migration and invasive ability of BC cell lines (T-47D and MCF-7). Furthermore, we analyzed the overlapping genes from our RNA-seq data and predicted targets from the mirDIP database, and twelve genes (ALDH1A3, FBN1, GRIA3, NOS1, PLD5, PTGER4, RASGRF2, RELN, RNF150, SLC17A4, TG, and TXNRD1) were identified as potential binding targets of miR-3614-5p in the current model. Nonetheless, only miR-3614-5p inhibition caused an increase in TXNRD1 expression upon Cd exposure in T-47D and MCF-7 cell lines. Importantly, luciferase reporter assays further verified that miR-3614-5p suppressed the expression of TXNRD1 by directly binding to the 3'-untranslated region (UTR), and TXNRD1 inhibition significantly repressed the proliferation and metastasis capacity of BC cells upon Cd exposure. Together, our findings demonstrated that Cd exposure repressed the expression of miR-3614-5p, thus activating TXNRD1 expression, which promoted the abnormal proliferation and metastasis of BC cells.
镉（Cd）被认为是一种内分泌干扰物，与乳腺癌（BC）的发生有关。我们最近的研究表明，Cd 诱导的 BC 进展与 miR-374c-5p 失调密切相关。我们的工作目的是研究其他可能参与 Cd 诱导的 BC 细胞增殖和转移的 miRNA。在我们的研究中，通过 miRNA-seq 分析了 Cd 处理的 T-47D 细胞（10μM，72h）的 miRNA 谱，我们的结果证实 miR-3614-5p 是下调最明显的 miRNA。此外，miR-3614-5p 模拟物转染显著降低了 BC 细胞系（T-47D 和 MCF-7）的增殖能力、迁移和侵袭能力。此外，我们分析了 RNA-seq 数据中的重叠基因和 mirDIP 数据库中的预测靶基因，确定了十二个基因（ALDH1A3、FBN1、GRIA3、NOS1、PLD5、PTGER4、RASGRF2、RELN、RNF150、SLC17A4、TG 和 TXNRD1）为当前模型中 miR-3614-5p 的潜在结合靶基因。然而，只有 miR-3614-5p 抑制会导致 Cd 暴露时 T-47D 和 MCF-7 细胞系中 TXNRD1 表达增加。重要的是，荧光素酶报告基因实验进一步证实，miR-3614-5p 通过直接结合 3'-UTR 抑制 TXNRD1 的表达，并且 TXNRD1 抑制显著抑制了 Cd 暴露时 BC 细胞的增殖和转移能力。总之，我们的研究结果表明，Cd 暴露抑制了 miR-3614-5p 的表达，从而激活了 TXNRD1 的表达，促进了 BC 细胞的异常增殖和转移。
